Interaction of Pregnancy-Specific Glycoprotein 1 With Integrin Α5β1 Is a Modulator of Extravillous Trophoblast Functions

TY - JOUR

T1 - Interaction of Pregnancy-Specific Glycoprotein 1 With Integrin Α5β1 Is a Modulator of Extravillous Trophoblast Functions

AU - Rattila, Shemona

AU - Dunk, Caroline E E

AU - Im, Michelle

AU - Grichenko, Olga

AU - Zhou, Yan

AU - Yanez-Mo, Maria

AU - Blois, Sandra M

AU - Yamada, Kenneth M

AU - Erez, Offer

AU - Gomez-Lopez, Nardhy

AU - Lye, Stephen J

AU - Hinz, Boris

AU - Romero, Roberto

AU - Cohen, Marie

AU - Dveksler, Gabriela

PY - 2019/10/31

Y1 - 2019/10/31

N2 - Human pregnancy-specific glycoproteins (PSGs) serve immunomodulatory and pro-angiogenic functions during pregnancy and are mainly expressed by syncytiotrophoblast cells. While PSG mRNA expression in extravillous trophoblasts (EVTs) was reported, the proteins were not previously detected. By immunohistochemistry and immunoblotting, we show that PSGs are expressed by invasive EVTs and co-localize with integrin 5. In addition, we determined that native and recombinant PSG1, the most highly expressed member of the family, binds to 51 and induces the formation of focal adhesion structures resulting in adhesion of primary EVTs and EVT-like cell lines under 21% oxygen and 1% oxygen conditions. Furthermore, we found that PSG1 can simultaneously bind to heparan sulfate in the extracellular matrix and to 51 on the cell membrane. Wound healing assays and single-cell movement tracking showed that immobilized PSG1 enhances EVT migration. Although PSG1 did not affect EVT invasion in the in vitro assays employed, we found that the serum PSG1 concentration is lower in African-American women diagnosed with early-onset and late-onset preeclampsia, a pregnancy pathology characterized by shallow trophoblast invasion, than in their respective healthy controls only when the fetus was a male; therefore, the reduced expression of this molecule should be considered in the context of preeclampsia as a potential therapy.

AB - Human pregnancy-specific glycoproteins (PSGs) serve immunomodulatory and pro-angiogenic functions during pregnancy and are mainly expressed by syncytiotrophoblast cells. While PSG mRNA expression in extravillous trophoblasts (EVTs) was reported, the proteins were not previously detected. By immunohistochemistry and immunoblotting, we show that PSGs are expressed by invasive EVTs and co-localize with integrin 5. In addition, we determined that native and recombinant PSG1, the most highly expressed member of the family, binds to 51 and induces the formation of focal adhesion structures resulting in adhesion of primary EVTs and EVT-like cell lines under 21% oxygen and 1% oxygen conditions. Furthermore, we found that PSG1 can simultaneously bind to heparan sulfate in the extracellular matrix and to 51 on the cell membrane. Wound healing assays and single-cell movement tracking showed that immobilized PSG1 enhances EVT migration. Although PSG1 did not affect EVT invasion in the in vitro assays employed, we found that the serum PSG1 concentration is lower in African-American women diagnosed with early-onset and late-onset preeclampsia, a pregnancy pathology characterized by shallow trophoblast invasion, than in their respective healthy controls only when the fetus was a male; therefore, the reduced expression of this molecule should be considered in the context of preeclampsia as a potential therapy.

KW - Cell Adhesion

KW - Cell Line

KW - Cell Membrane/metabolism

KW - Cell Movement

KW - Extracellular Matrix/metabolism

KW - Female

KW - Focal Adhesion Protein-Tyrosine Kinases/metabolism

KW - Heparitin Sulfate/metabolism

KW - Humans

KW - Immobilized Proteins/chemistry

KW - Integrin alpha5beta1/metabolism

KW - Placenta/metabolism

KW - Pre-Eclampsia/diagnosis

KW - Pregnancy

KW - Pregnancy Trimester, First

KW - Pregnancy-Specific beta 1-Glycoproteins/analysis

KW - Protein Binding

KW - Trophoblasts/cytology

U2 - 10.3390/cells8111369

DO - 10.3390/cells8111369

M3 - SCORING: Journal article

C2 - 31683744

VL - 8

JO - CELLS-BASEL

JF - CELLS-BASEL

SN - 2073-4409

IS - 11

ER -